Chemopreventive effect of aspirin on growth of aberrant crypt foci in rats

Nonsteroidal anti-inflammatory drugs display a chemopreventive effect on polyps and cancer of the large bowel. This study evaluated the inhibitory effect of aspirin on the distribution and growth of aberrant crypt foci (ACF), the earliest putative preneoplastic and early neoplastic lesions in a rat model. For initiation of ACF, Sprague Dawley rats were injected with azoxymethane (30 mg/kg), a well-established rat carcinogen. After the second injection the rats were allocated to three groups, which received 0.2% or 0.6% aspirin or the solvent only (control group). After 6 weeks the animals were killed, and their colons removed, fixed in formalin, and screened for distribution and size of ACF, separately for middle and distal parts of the large intestine. The rats injected with azoxymethane showed a 100% incidence of ACF. Administration of 0.2% and 0.6% aspirin resulted in 55% and 54% reduction, respectively, in overall frequency of ACF. Aspirin significantly reduced the frequency of medium-sized (four to six crypts per focus) and large (three to six crypts per focus) but not the small (one to three crypts per focus) ACF. In the control group the ACF of the same multiplicity were larger than those in the aspirin-treated rats. No statistically significant difference in ACF-inhibiting effect was noted between 0.6% and 0.2% aspirin solution. Aspirin given at a concentration of either 0.2% of 0.6% thus has a chemopreventive effect on ACF, acting on postinitiation stage of azoxymethane-induced colonic carcinogenesis model in rats.